In the past, jugular bulb venous oximetry has been used to provide a global overview of the dynamic relationship between brain oxygen delivery and demand in certain acute neurological disorders. However, the invasive nature of this method as well as the lack of regional specificity have limited the scope of its application in clinical practice. It is critical important to be able to accurately assess and quantify the relationships between oxygen supply and oxygen demand on a regional basis, so that the pathophysiology of acute stroke and related disorders can be investigated. In this proposal, we will test the general hypothesis that the oxygen saturation of venous blood within the brain parenchyma can be measured, in absolute terms, using advanced magnetic resonance imaging (MRI) techniques. Specifically, the MR signal intensity changes induced by the presence of deoxyhemoglobin within the cerebral vasculature will be measured using a novel gradient/spin echo sequence. High resolution maps of regional cerebral blood volume (rCBV) will also be measured using a three-dimensional steady state MRI method. Combining information from these two imaging sequences, the oxygen saturation of blood within the brain parenchyma can be estimated. We will first validate the proposed MRI methods by testing their ability to accurately predict the oxygen saturation of blood within the brain parenchyma of the rat under a wide variety of pathophysiologic conditions. The validation process will be carried out using well established physiologic manipulations that produce global changes in cerebral blood oxygen saturation and rCBV. These will include acute hemorrhagic hypotension, hemodilution, alterations of arterial carbon dioxide tension, and hypoxemia. These experimental paradigms lend themselves to direct comparison with the gold standard used throughout the project-the oxygen saturation of jugular venous blood samples. Finally, well characterized rat models of focal ischemic injury will be used to investigate the regional applicability of the proposed methods. The success of this proposal should provide the opportunity to non- invasively measure the oxygen saturation of blood within the brain parenchyma on a regional basis with high spatial resolution. This capability could introduce a widely available means for monitoring the dynamic pathophysiology of altered oxygen delivery, and the brain's response to certain therapeutic interventions.